Chalcone dichloride and insecticidal compositions thereof



CHALCONE DlCHLOR-IDE LAND INSECTIQIDA'L COMRQSITIQNS THEREOF samueir. can, University, Miss.

No Drawing Application December 20, 1951',

. SerialNo. 262,659;

4 Claims. (Cl. 1671-30) Thisinvention relates to 'chalcone dichloride and certain of its derivatives: It isdirected particularly to a-new class of. compounds which is toxic to living matter, suchas and insects, and suitable cause as economic poisons;

Theinsecticidalvalue of chlorinated hydrocarbons is well recognized. One of the most 1 widely known mem-' bers of this group is 2,2-di(4-chlorophenyl)-1,l,l-trichloroethane (hereinafter referred to as DDT). Furthermore, some species of insects develop a remarkable resistance to some of these chlorinated hydrocarbons.

In attempting to solve the problem of increased insect resistance it has been claimed that the combination of certain chlorinated hydrocarbons with other compounds isrnoreefiective than the respective chlorinated hydrocarbons alone. Suchcompounds include carbinols, esters, ethers, hydrocarbons, chlorinated hydrocarbons andiu-nsaturated ketonesr One'of the objects of the presentinvention is-to make available a new class of useful compounds. Another object of the invention is to provide compounds which are useful as toxicants for living matter, such as fungi and insects. A further object of the invention is to provide new compounds with characteristics such that they disrupt the normal metabolic processes of living organisms, thereby having a toxic effect directly, or so change the resistance of the organisms so that othertoxic materials may become eifective;

This invention is directed to the making and using of chlorinated aromatic ketones containing the special groupmg:

suitably, enclosed; by unsubstituted, or substituted, aromatic.rings,.which, in summation, render the'members ofthe classeffective as economic poisons; Such. aromatic rings and alkyl-substituted rings include anthryl, furyl, naphthyl, phenanthryl, phenyl, thiofuryl, tolyl, Xenyl and xylyl groups. Rand R maybe. either ahydrogen atom or an alkyl group. Certain members of this class of compounds appear to be particularly effective synergists in compositions containing chlorinated hydrocarbons, suchasDDT, against strainsof insects resistantto such chlorinated hydrocarbons.

More specifically, the present invention is directed to chlorinated aromatic ketones-having the general formula wherein R1 and R2 are members of the class consisting of an aromatic ring and a chlorinated aromatic ring, and R3 andR4 are members of the class consisting; of hydro- I, Patented Sept. 1957 a 2 a. gen andsan-alkyl' -groupt Fourteencompounds representative of this class are:

'1,3rdiphenyl12,3dichloro-l-propanone l,3-di(4-chlorophenyl) -2,3-dichloro-1-propanone 3 (4-chlorophenyl') -l-phcny1-2,3-dichloro-l-propanone 3-(2,"4 -dichlorophenyl') 1' phenyl 2,3 dichloro-l-propanone 3-(2-chloropheny1) 1 -(4-chlorophenyl)-2;3-dichloro-1- propanone 1,3-di(4-t0lyl)-2,3-dichloro-1-propanone 1,3-di-((4-chlorophenyl) 2,3 dichloro-Z-methyl-l-propanone 1,3-diphenyl-2,3 dichloro=3-methyl-l-propanone- 1-fi-naphthyl-3,-phenyl-2,3-dichloro-1-propanone 3-(4-chlorophenyl), 1 0L naphthyl 2,3edichloro11-pro panone 3t-'P h'eny1-1 prxenyl2,3;dichlororl-propanone 3 4 -.chlorophenyl) =1 p-xeny1-2,3-dichlorc-l-propanone. 3;u-furyl-l:phenyl-2,3V-dihloro-l-propanone 3'-*pl1'enyl-la-thieny112,3rdichloro-l-propanone The chlorinatedtaromatic ketonesof the present-inventiom without. :alkyh substituents fon hydrogensinthe prop anoneahaver-thageneral formula wherein-Rrand R2 are-members of the classpconsisting of" anaromat-ie ring and a' chlorinated aromatic ring. Twelvecompounds representative of thisclassification include all of thoselisted-in the-preceding paragraph, except 1,31-di-(4-chlorophenyl) 2,3,- dichloro 2-methyl-l-pror panone, and i 1,3-diphenyl-2,3-dich1oro 3-methyl-1-propanone The-chlorinated aromatic ketones of the present-invention with chlorine-substituentsin the-terminalaromatic rings have th'egeneral formula Bi RA R1 & CO R2 wherein R1 is a chlorinated aromatic ring; R2 is amember of the class consisting ofran aromatic ring and a chlorinated aromatic ring,.and Raand R4 are members of .the class consisting offhydrogen and an alkylgroup. Seven compounds"representative of this class are 3 -(4-chlorophenyl)-1-plrenyl:2,3rdichlcroelepropanonefl 3-. 2,4-dichlorophenyl -1phenyl 2,3=dichloro l-propanone B-(Z-chlorophenyl) 1 (4-chlorophenyl)-2;3'-dichloroel+ propanone 1, 3-di-(4-chloropl1enyl) 2,3 dichloro 2:- methyl-l-propanone- 3+(4.chlorophenyl) 1 u;- naphth-yl 2,3-dichloro-1-propanone;

3- (4e-chlor0phenyl) -1p -xenyl-2, 3 -dichloro.-1-propauone,

None of the compounds givenin the threepreceding paragraphs has been known hitherto, with the exception of the parent compound, chalcone dichloride (1,3-diphenyl-2,3-dichloro=l-propanone). Therefore, each of the new compounds has been prepared for the first time to make itavailable fortesting. The class of compounds for which the general formula and representatives are given in the preceding paragraph include some compounds which haveb'een foundto be the most effective synergists with" chlorinated hydrocarbons, such' as DDT.

Onegeneral methodformaking the compounds oft-he present invention involves (-1) "the condensation of unsubstituted or substituted aromatic aldehydes and ketones, or ketones alone, to form unsaturated ketones, and (2) the chlorination of such unsaturated ketones. These process steps are illustrated by the following equations;

The condensations may be effected with basic catalysts, such as alcoholic sodium hydroxide or sodium ethylate, or by acidic catalysts, such as dry hydrogen chloride or boron trifluoride, in the presence or absence of solvent. The preferred temperature range is from 20 C. to the boiling point of the solvent, which is frequently ethanol (B. P. 78 (3.), although temperatures up to that of the lowest boiling reactant are desirable in certain cases. The reactions are carried out most advantageously at atmospheric pressure, or moderately above for larger scale production. The products may be recovered by precipitating them on pouring the reaction mixture into water or by vacuum evaporation of the unreacted starting materials. Neutralization of the catalyst may be efiected before either of the recovery operations is undertaken. Purification may be accomplished by alcohol and water washing.

The chlorination step is performed preferably by dissolving the unsaturated aromatic ketone in a suitable solvent, such as acetic acid, benzene or chloroform, and then passing chlorine into the solution until the unsaturated ketone has been substantially completely saturated. The preferred temperature range is from C. to the boiling point of the solvent with the pressure usually employed being slightly greater than atmospheric pressure' The recovery of the product is obtained by evaporation of the solvent or, in the case of a water-soluble solvent, by precipitation with water.

Examples illustrating the method for preparing representative members of the class of compounds of the present invention are given below. j

Example I A mixture of 1130 g. (8.1 moles) of p-chlorobenzaldehyde and 1251 g. (8.1 moles) of p-chloroacetophenone was poured with shaking into a 12-liter round bottom flask containing 36 g. of sodium hydroxide dissolved in 300 ml. of water and 70 ml. of ethanol. The mixture became hot, and solidification took place in about 15 minutes. After standing 48 hours, the solid mass was treated with 1000 ml. of water and was then broken up. The suspension was neutralized with dilute hydrochloric acid and was filtered. The solid product was washed with water, with a 50% aqueous solution of ethanol, and again with water. The air-dried crude 4,4'-dichlorochalcone weighed 2195 g. (95.5% yield). A sample recrystallized from ethanol melted at 154-6" C.

A solution of 47 g. (0.13 mole) of recrystallized 4,4- dichlorochalcone in 950 ml. of chloroform was placed in a 3-neck flask equipped with a sparger tube for chlorine admission, a thermometer, and a reflux condenser, which in turn was connected to a water bubbler to keep the system under a pressure of three inches of water. 'Chlorine was passed in at a moderate rate over a period of 24 minutes until saturation was achieved. The color of the solution changed from a light yellow to the characteristic yellowish-green of chlorine solutions when saturation was complete. The temperature rose. from 23 to 39 C.;

during the addition of the chlorine. The condenser was reset for distillation, the sparger tube was removed and replaced with a stopper. The distillation was interrupted when the collected distillate reached a volume of 870 ml. (boiling range, 47 to 62 C.) and 90 ml. of ethanol was added to the colorless residual solution. Upon cooling and filtering, a yield of 45.5 g. (77.1%) of 1,3-di(4- chlorophenyl)-2,3-dichloro-l-propanone, white crystals with M. P. 144-5 C., was obtained. An additional quantity of light yellow, partially solidified substance was obtained on evaporation of the filtrate to dryness. However, the weight of this second fraction brought the total 1 yield to more than 100%, indicating the retention of prepared by the preceding chlorination procedure.

Example 11 Using the procedure of Example I, 28.1 g. (0.2 mole) of p-chlorobenzaldehyde was condensed with 24 g. (0.2 mole) of acetophenone in the presence of 6 g. of sodium hydrom'de dissolved in 40 ml. of water and 20 ml. of ethanol. The yield of 4-chlorochalcone (M. P. l08-ll C.) was 42 g. (86.2%). A 10-g. sample of this intermediate was dissolved in 30 ml. of chloroform, and the solution saturated with chlorine. A yield of 5.3 g. (41%) of 3 (4 chlorophenyl l phenyl) 2,3 dichloro l propanone (M. P. 1586l C.) was obtained.

Example 111 Using the procedure of Example I, 35 g. (0.2 mole) of 2,4-dichlorobenzaldehyde was condensed with 24 g. (0.2 mole) of acetophenone in the presence of 6 g. of sodium hydroxide dissolved in 40 ml. of water and 20 ml. of ethanol. The yield of 2,4-dichlorochalcone (M. P. 62- 5 C.) was 35 g. (63.1%). A 10-g. sample of the chalcone was dissolved in 50 ml. of chloroform, and the solution saturated with chlorine. A yield of 4.6 g. (37%) of 3-(2,4-dichlorophenyl)-1-phenyl-2,3-dichloro-1-propa none (M. P. 99-101 C.) was obtained.

Example IV Using the procedure of Example I, 45.7 g. (0.325 mole) of o-chlorobenzaldehyde was condensed with 50.3 g. (0.325 mole) of p-chloroacetophenone in the presence of 6 g. of sodium hydroxide dissolved in 50 ml. of water and 25 ml. of ethanol. The yield of 2,4-dichlorochalcone (M. P. 78-80" C.) was 80 g. (88.3%). A 10-g. sample of this chalcone was dissolved in chloroform and chlorinated. A yield of 5.6 g. (45.9%) of 3-(2-chlorophenyl)-' 1-(4-chlorophenyl) -2,3-dichloro-l-propanone (M. P. 101- 4 C.) was obtained.

Example V Using the procedure of Example I, 24 g. (0.2 mole) of p-tolualdehyde was condensed with 26.8 g. (0.2 mole) of p-methylacetophenone in the presence of aqueous-alcoholic solution of sodium hydroxide. The yield of pale yellow, crystalline 4,4-dimethylchalcone (M. P. 128-9" C.) was over 80% of theoretical. A sample of this chalcone was dissolved in chloroform, and the solution was saturated with chlorine. A white crystalline solid, 1,3-di- (4-tolyl)-2,3-dichloro-l-propanone, was obtained as the product (M. P. 132-4 C.).

Example VI Using the procedure of Example I, 14 g. (0.1 mole) of ,p -chlorobenzaldehyde -,was. ;conde nsed with 16 .8;;g. 0.1 mole) f ers mn pr l a ne nt e Pressneestmdium ,ethylate in. ethanolic; solution. ,Ih6fl,4-' -dil11QE9-d-,D1Qthylchalcone obtainedwas-dissolved in chloroform; andchlo- .rinatedtogivea white, crystalline solid,:1,3+.di -(;4.-ch1oro- .,-phenyl) 2,3- dichloror2-methyll prgpanone.

Example V-H Dypnone, produced fromracetophenonesbyathegproce- .dure .of Example. I. withsodi lm .methylate ;as .the; catalyst, .was chlorinated in .chloroformsolution .toyield 'dypnone dichloride, or .1,3:diphenyl 2,3. dichloro 3 -rnethyl-1;propanone.

:EW'Z PI l ll Using theproceduree of Examplelfltl-o g. (0.-1--mole) of 'ben-zaldehyde .was 1 condensed with 17- g; 0. 1 mole) of methyl fi-naphthyl ketone in the presence of sodium hyd-roxide'in aqueous-alcoholic*solution. Theproduct, oc-

'- benzabZ-acetonapht-hone,was isolated as-red-goldcrystals (M. P. 105-6 C.). A sample of the latter was dissolved 'inchloroform and chlorinated to awhite solid, l fi-naphthyl-3-phenyl 2,3-dichloro-l propanone.

Example IX Example X Using theuproce'dur of Example I, 10.6 g f (0i 1 mole) -of-benzaldehyrle was-condensedwith 4 9. 6 g.- 0; 1- mole) of p-phenylacetophenone in the presenceof alcoholic -potassium hydroxideto give -yellow .crystals:o'f"4f-phenylchalcone (M. P. 1556 C.). A sample of the latter was dissolved in chloroform and chlorinated to give 3-phenyl-1- p-xenyl-2,3-dichlor.o l propanone.

.Example XI Using the, procedure ofExample I, 14 g. (0.1mole) .of p-chlorobenzaldehyde was condensed with 19.6 g. (0.1 mole) of p-phenylacetophenone in the presence of sodium ethylate to yield 4-chloro-4'-phenylchalcone. A sample of the chalcone was chlorinated in chloroform solution to yield a white solid, 3-(4-chlorophenyl)-1-p-xenyl-2,3-dichloro-l-propanone.

Example XII Using the procedure of Example I, 9.6 g. (0.1 mole) of furfural was condensed with 12 g. (0.1 mole) of acetophenone in the presence of aqueous alcoholic sodium hydroxide to yield an oil, furfurylideneacetophenone (B. P. 315-8 C. at 760 mm). This intermediate was dissolved in chloroform and chlorinated to yield 3-a-furyl-1-phenyl- 2,3-dichloro-l-propanone.

Example XIII Using a modification of the procedure of Example I, 10.6 g. (0.1 mole) of benzaldehyde was condensed with 12.6 g. (0.1 mole) of methyl a-thienyl ketone in the presence of dry hydrogen chloride to yield styryl a-thienyl ketone (M. P. 7980 C.). A sample of the latter was chlorinated in chloroform to give 3-phenyl-1-a-thienyl- 2,3-dichloro-1-propanone.

The toxicants of the present invention may be prepared and dispersed in comminuted form with or without inert diluents and/ or wetting or spreading agents, or dispersed in a suitable medium either in the form of an emulsion or in solution of a suitable solvent or mixture of solvents. The lower melting point members of this class of chlorin- 6 ated-aromatic,ketonqsrthat ieqwithr neltingmoints .of the order of 100 to 125 C., maybe-used.astumigantsas wellascontacticides.

DDTlisone ,ofithe chlorinated hydrocarbons which has bee i general use foma-tsufilcifinttnumbeniofw'yfiars to observesthat .certain insects, such as the domestic fly ...Mascatdomestica.develop st in ich haile ec me a most completely resistant to the action of DDT.

One possible soluftion'joflthe problern..of increased resistanceto toxic eflfectistosubstitute-thenewer-chlorinated hydrocarbons as contacticides-for'DDTn'esistant -house flies. Gne of the newerinsecticidesfrorrr the' standhexachlorocyclohexane, which is not only a' powef-ful 1 insecticide --but' 3150 3 -persistent fumigant. However; this substitutionprocedurhas not been-too satisfactory since certain strains of insects -WeIe -ii'llli2il-ly -re'sistant,-or --very rapidly developed resistance to the -newer toxicants.

Gertaintests made todeterrnine. the toxicity of -the =new class of chlorinated -aror-natic ketones of -the present invention,particularly to ascertain both' qualitatively-and quantitatively-the responseef the house fly,- Musca d0- 2 mestz'ca, to -a =mixture i of the respective compound with "DDT-aremepresented by the-examples given'below.

Example XIV :Qne zseries of:;teststwasrmadeswonna =strain offDDT irresistant; flies, 1M usca; damesticajs Roberd; zbytrobserving the efiectiofitopiwl zapplicationxof a solution .of:.the 1 compound .ilidicatcd-andiaDDTginaanzinert solvent. 'uEach fly.'was anesthetizedvwith:carbonedioxide, 1a.; drop of :theztoxicant -solution-was supported on a small-.wire loopyand a small amount;- ofzthe. rsoliltiona WaSJEaPPljEd-idjIGCtIY.01'1' theback or jthoraxi ofzathezcfly. ,ia hpproximately: SOfliesaWere' used ffor icach'lesta andrthejfemale mortalitywas recorded.

is given for a mixture of DDT and 1,3-di(4-chlorophenyl)- 2,3-di-chlorol-propanone present in a 10:1 ratio. The two materials were dissolved in methyl ethyl ketone, the solution was applied to poster boards in such a manner as to provide a residual coating of 200 mg. and 20 mg. per square foot, respectively, and the residual coating allowed to age for one week. The flies were exposed to the toxicants on the poster boards for two hours and then observed after a period of 24 hours had elapsed. The adult female mortality was 92% for the combination as compared with 0% in the case of the control (DDT residue only but otherwise identical conditions).

Example XVI A further example of the eflect on DDT resistant flies is given for various ratios of DDT and 1,3-di(4-chlorophenyl) -2,3-dichloro-l-propanone by contact with older residual deposits. Solutions of the two materials in appropriate proportions were applied to the plywood walls of respective test cages in such a manner as to provide residual deposits of 200 mg.:200 mg, 200 m.:40 mg, and 200 mg.:20 mg. per square foot, respectively. After a four-week aging of the deposits and a 30-minute exposure of the flies to the aged deposits, the adult fly ture and reactive functional groups.

mortalities at the end of the 24-hour period after exposure were observed and recorded.

DDT-Oompound Ratio, mg./sq. ft.

Male Female The series of compounds described above was developed as a group of insecticides with effective patterns of struc- The structure of the unchlorinated, unsaturated ketones is similar to that of chalcone, its naturally occurring derivativesthe polyhydroxychalcones, and its related classes-the fiavones and the fiavonols. Saturated ketones of similar structure, the flavanones, are also known to'occur in nature. Suitable modification of these basic structures so familiar in nature by the introduction of potential reactive centers may be deleterious to the normal enzyme systems of insects.

It is now generally recognized that certain insects develop resistance to the lethal action of chlorinated hydrocarbons, and that this resistance, though developed against one chlorinated hydrocarbon, is nevertheless effective toward others. The process of detoxifying DDT, in the case of house flies, is apparently one of dehydrohalogenation to form 2,2-di(4-chlorophenyl)-1,1-dichloroethene, a compound isolated in significant quantityfrom the bodies of resistant strains of flies exposed to DDT.

The efiectiveness of the present series of chlorinated aromatic ketones with the chlorinated hydrocarbon, DDT, indicates their potential effectiveness when used with other toxicants, such as aldrin, chlordane, dieldrin, lindane and toxaphene.

Furthermore, the characteristics of the present series of chlorinated aromatic ketones are such that their manner of use, either alone or in combination with other toxicants, includes all typical methods for the applications of insecticides, such as solutions and emulsions for brushing or spraying, dry powders for dusting, wettable powders for preparing emulsions and suspensions, arid distribution as a fumigant.

Fly Mortality, Percent pounds described and claimed, the applicant has adopted one of the well-recognized classifications as set forth by Gilman'in his Organic Chemistry, vol. 1, 52-149 (1938). In chapter 2, Theory of Structure and Reactions of Aromatic Compounds, the term aromatic compounds includes benzenoid rings and heterocyclic rings exhibiting raromatic character, and specifically includes pyridine, pyrrole, thiophene, pyrazole and furan.

The, present invention is directed generically to compounds consisting of and compositions of matter comprising alpha, beta-dichloropropanones containing aromatic suhstituents in the 1,3-positions. t

In the respective species described and claimed, the aromatic substituents are:

1. Unsubstituted and chloroand alkyl-substituted benzene rings.

.cides and fumigants. The use of the term in the claims makes it possible to eliminate possible objection to al- .ternatives and multiplicity of claims.

I claim: p 1. An economic poison comprising 1,3di(4-chloro phenyl) -2,3-dichloro-1-propanone. Y

2. An insecticide comprising a chlorinated insecticidal hydrocarbon and 1,3-di(4-chlorophenyl)-2,3-dichloro-1- propanone.

3. An insecticide comprising 2,2-'di(4-chlorophenyl)- 1,1,1-trichloroethane and 1,3-di(4-chlorophenyl)-2,3-dichloro-l-propanone. 4. 1,3-di (4-chlorophenyl)-2,3-dichloro-l-propanone.

References Cited in the idle of this patent UNITED STATES PATENTS Re. 22,922 Muller Sept. 30, 1947 2,282,907 Horst May 12, 1942 Thompson May 22, 1951 

2. AN INSECTICIDE COMPRISING A CHLORINATED INSECTICIDAL HYDROCARBON AND 1,3-DI(4-CHLOROPHENYL)-2,3-DICHLORO-1PROPANONE. 